The present invention relates to the technical field of sterilization of medical containers, such as medical instruments, ampoules, tubes or the like.
In particular, the present invention relates to a method for thermal sterilization in particular of a container filled with medical material or product, the thermal sterilization being carried out in particular in the presence of a sterilization atmosphere containing steam or under the influence of wet heat.
Furthermore, the present invention relates to the containers, which are obtained according to the method according to the invention, filled with medical material or product and in particular are tubes, ampoules and medical instruments such as e.g. syringes, and to the sterilized filled containers provided in packaging.
Within the scope of the present invention, the term “sterilization” is understood to mean the killing or irreversible inactivation of all microorganisms and viruses, including their rest states, such as e.g. endospores, which are situated on or in an object. Since complete inactivation of all microorganisms and viruses on or in an object cannot be ensured with absolute certainty, an object or a unit of sterilization goods generally counts as sterile if the probability of contamination with microorganisms or viruses that are able to reproduce is no more than 1:106. This means that of one million units of the sterilization goods, at most one unit is contaminated by a colony-forming unit (CFU) of a microorganism or that the remainder of microorganisms or viruses that are able to reproduce is no more than 10−6 colony-forming units (CFUs) per unit of the sterilization goods. The remainder of at most 10−6 colony-forming units per unit of sterilization goods is also referred to as sterility assurance level (SAL).
Depending on the type of sterilization goods, different sterilization methods are available, which are distinguished according to chemical and physical sterilization methods.
By way of example, chemical sterilization methods include gassing with formaldehyde or ethylene oxide; however, these are connected with high costs and great methodological-technical expenditure, are only suitable for specific applications as a result of the risks involved in using substances that are hazardous to health and the use of these compounds is not always possible for regulatory reasons. Thus, for example, ready packaging in which the goods to be sterilized are packaged must be permeable to the sterilization gases. However, it must furthermore also be ensured that the gases can once again be completely removed after the sterilization is completed; this proves very difficult in practice. Alternatively, the sterilization goods are sterilized unpackaged, and must subsequently be packaged under sterile conditions, for example in cleanrooms; this increases the complexity and the costs involved in carrying out the method.
Moreover, these methods are not suitable for sterilizing goods stored in sealed containers because no contact can be produced between the sterilization gas and the potential sterilization goods.
Thus, physical methods are generally preferred when selecting the sterilization method if the materials or goods to be sterilized are stable under sterilization conditions. Physical methods have particularly proven their worth in the case of sterilizing packaged sterilization goods or sterilization goods which are situated in sealed containers.
Physical sterilization methods are subdivided into actinic methods, in which the microorganisms are killed or irreversibly inactivated by ionizing radiation, and thermal methods, which are based on thermal exposure.
By way of example, actinic methods include irradiation by UV, gamma or electron beams, which are for example utilized in the industrial production of medical disposable articles.
By contrast, the sterilizing effect of the thermal methods is based on the heat-induced denaturing of proteins, which, along with their native structure, also lose their biological capabilities and effects, resulting in the killing or irreversible inactivation of the microorganisms.
The thermal sterilization methods include, in particular, the hot air sterilization and the steam sterilization, with the hot air sterilization only being suitable for a few applications as a result of the poor reproducibility and the sensitivity towards very small deviations from the ideal method progress, caused by the poor heat transfer of the air.
By contrast, steam sterilization is the “gold standard” of sterilization methods, in which the sterilization goods are as a standard heated by steam at 121° C. and with an overpressure of 2 bar absolute for 15 minutes to a temperature of 121° C. This sterilization method, synonymously also referred to as “saturated steam method”, is outstandingly reproducible and automatable and is also suitable for sterilizing goods packaged in sealed containers.
Although the steam sterilization methods have proven their worth in everyday practice and are based on mature technology, the long duration often required for sterilization is disadvantageous; this makes it more difficult to carry out an economically expedient sterilization and increases the costs of actually carrying out the method and, subsequently, of the sterilized products as well. This particularly holds true against the backdrop that steam sterilizations are generally carried out discontinuously in autoclaves. The undesired occurrence of thermal instabilities is also possible.
Shortening the sterilization time, i.e. a more effective sterilization, would lead to a higher throughput and hence to a more economical way of carrying out the method. However, the sterilization temperature would have to be increased significantly for this, which would in turn significantly restrict the selection of sterilization goods to which this method can be applied because plastics in particular can react very sensitively to a temperature increase under the application of humid heat.
Moreover, the conventional steam sterilization methods are disadvantageous in that the amount of energy introduced into the sterilization chamber by the steam is not utilized efficiently. Hence, a large proportion of the energy introduced into the sterilization chamber always remains unutilized as a result of uncondensed steam during steam sterilization methods.
The application of the saturated steam method is primarily restricted by the sensitivity of the materials to be sterilized to humidity and heat. The high effectiveness and efficiency of the saturated steam method is based on the large amounts of energy that are transferred by the steam. Thus: water at 121° C. and a pressure of 2 bar has an enthalpy of vaporization, which is also referred to as latent heat, of 2.199 kJ/kg. When the steam condenses on the cooler sterilization goods, this amount of heat is transferred to the sterilization goods and, if applicable, to the microorganisms situated thereon, as a result of which, firstly, microorganisms are killed or irreversibly inactivated directly and, secondly, sealed containers can be heated such that the contents thereof can also be sterilized—subject to sufficient thermal conductivity and heat transfer in the interior of the container.
Modified steam sterilization methods are applied in the case of sterilization goods, in particular in the case of sealed containers, in the interior of which pressures may build during or, in particular, after the sterilization, more particularly as a result of the filling thereof, which pressures exceed the pressure of the surrounding steam atmosphere. These methods generally do not operate with saturated steam, but rather with steam/air mixtures. As a result of the lower amount of energy in the steam/air mixtures compared to pure steam, these methods are generally carried out in accordance with the standard saturated steam method, which means that steam sterilizations using steam/air mixtures are carried out using longer sterilization times and the sterilization success or the sterilization time is converted to standard conditions (i.e. pure steam at 121° C. and 2 bar absolute) for simpler comparison.
Thus, EP 0 703 793 B1 describes a method for producing sterile ready packaging, with sealed, more particularly blister packed, containers situated therein, more particularly syringes, that are filled with medicines. The sterilization is brought about by means of saturated steam, with the pressure in the sterilization apparatus being increased by means of compressed air during the cooling procedure.
WO 2009/018948 A2 also describes a sterilization method, the disclosed method being intended to be used to sterilize groups of objects and the sterilization taking place by means of steam/air mixtures.